The primary objectives of our program are to obtain an improved understanding of the mechanisms responsible for selected disorders of cardiovascular function and the actions of pharmacological agents and, through this approach, to develop improved means for diagnosis, prevention and treatment. We approach this goal through basic and clinical investigations on the heart and vascular system using the techniques of electrophysiology, physiology, pharmacology, biochemistry, and in selected studies, ultrastructural analysis. The research is conducted in the following areas: I: Electrophysiological Basis for Disturbances of Cardiac Rhythm and Conduction and the Action of Cardiac Drugs; II: Role of the Autonomic Nervous System in Cardiovascular Regulation and its Importance in Disease; III; The Pharmacology and Toxicology of Antiarrhythmic Agents and the Diagnosis and Management of Arrhythmias; IV: Studies of Patients During and After Open-heart Surgery; V: Studies in the Cardiac Surgical Laboratories; VI: Electrophysiological and Structural Basis for Ischemic Arrhythmias; VII: Pediatric and Developmental Cardiac Electrophysiology and Pharmacology; VIII: Animal Models of Arrhythmias; and IX: Cardiovascular Regulation and Circulatory Control. A related objective of the proposed studies is to develop through continuing collaboration between basic scientists and clinical investigators, a more rapid and thorough interchange of information and techniques so that important clinical problems can be identified and subjected to intensive study and so that new methods and information developed in the laboratory can be rapidly evaluated and applied to diagnosis and patient care. The Supplemental Application is designed to increase our capabilities to study cardiac activation during arrhythmias and to add several new studies which are logical and necessary extensions of ongoing work.